pharmacokinetics of ssp-004184 in the treatment of chronic iron overload requiring chelation therapy

Conditions: Iron Overload Due to Repeated Red Blood Cell Transfusions

Summary: the purpose of this study is to evaluate ssp-004184aq in patients with transfusional iron overload whose primary diagnosis is hereditary or congenital anemia. ssp-004184aq is an iron chelator under development for chronic daily oral administration to patients with transfusional iron overload.


Eligibility criteria:
inclusion criteria: * willing and able to sign the approved informed consent. * age: 18-60 years old, inclusive, at screening. * subjects who have received more than 20 transfusions in their lifetime and who have transfusional iron overload requiring chronic treatment with an iron chelator. n.b.: sickle cell disease subjects receiving regular exchange transfusions and iron overloaded subjects with thalassemia intermedia who are receiving regular transfusions (transfusion dependent thalassemia intermedia) are eligible. * willing to discontinue all existing iron chelation therapies for a minimum period of one to five days prior to first dose of ssp-004184aq, the 24 week duration of the study and 1 week after last dose for a total of approximately 26 weeks. * willing to fast two hours prior to and one hour after each dose. * serum ferritin \>500ng/ml at screening. * baseline liver iron concentration is greater than or equal to 5mg iron per g (equivalent dry weight, liver)determined by ferriscan® r2 mri. * mean of the previous three pre-transfusion hemoglobin concentrations is greater than or equal to 7.5g/dl. * adult female subjects should be: 1. post-menopausal (12 consecutive months of spontaneous amenorrhea), or 2. surgically sterile, or 3. females of child-bearing potential must have a negative beta-hcg pregnancy test at the screening visit and a negative urine pregnancy test at the baseline visit. females of child-bearing potential must agree to abstain from sexual activity that could result in pregnancy or agree to use acceptable methods of contraception. exclusion criteria: * as a result of medical review, physical examination, or screening investigations, the principal investigator (pi) considers the subject unfit for the study. * non-elective hospitalization within the 30 days prior to baseline testing. * evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, biliary, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow, or skin disorder that contraindicates dosing with ssp-004184aq. * iron overload from causes other than transfusional siderosis. * evidence of severe renal insufficiency, eg, serum creatinine 1.5x above the upper limit of normal or proteinuria greater than 1 gm per day or a calculated glomerular filtration rate \<60ml/min. * severe iron overload including: 1. t2\* mri \<10 ms 2. liver iron concentration by ferriscan r2 mri \>30mg/g liver (dw) * known sensitivity to magnesium stearate, croscarmellose sodium or ssp-004184aq. * platelet count below 100,000/μl or absolute neutrophil count less than 1500/mm3 at screening. * insufficient venous access that precludes prescribed blood draws for safety laboratory assessments. * alt at screening \>200 iu/l. * use of any investigational agent within the 30 days prior to the baseline testing. * pregnant or lactating females. * cardiac left ventricular ejection fraction 1. below the locally determined normal range in the 12 months prior to screening by echocardiograph or mri or 2. \<50% at baseline testing by mri (echocardiograph is acceptable for lvef if mri information is not available).